The respiratory tract and intestinal tract are common sites for infection by pathogens. Despite the host organism often having a functioning immune system, the respiratory and intestinal tract frequently become infected because they are in direct contact with the physical environment and are exposed to pathogenic microorganisms (such as viruses, bacteria, protozoa, fungi, etc.) that can be transmitted e.g. by touch, in the air and via food. There are many microorganisms that cause illness in infants and other individuals. For individuals whose immune systems are compromised the risk of infection and serious illness is even higher.
Respiratory syncytial virus (RSV) is the leading cause of serious lower respiratory tract disease in infants and children. Primary RSV infection occurs most often in children from 6 weeks to 2 years of age. RSV is estimated to cause as much as 75% of all childhood bronchiolitis and up to 40% of all pediatric pneumonias. Children at increased risk from RSV infection include preterm infants and children with bronchopulmonary dysplasia, congenital heart disease, congenital or acquired immunodeficiency and cystic fibrosis. The fatality rate in infants with heart or lung disease who are hospitalized with RSV infection is 3%-4%. Treatment options for established RSV disease are limited. Severe RSV disease of the lower respiratory tract often requires considerable supportive care, including administration of humidified oxygen and respiratory assistance.
Epidemiology studies also show that the incidence of asthma and allergy in children up to 12 years of age is considerably higher in children who have been hospitalized as infants with RSV infection.
Acute otitis media (AOM) is the most frequent diagnosis in physician offices among children 1-4 years of age. There is strong correlation between the presence of virus in the nasopharynx and the occurrence of otitis media; using sensitive molecular testing methods (eg PCR), respiratory viruses have been detected in up to 90% of cases. RSV, adenoviruses and influenza virus are most frequently seen; RSV accounts for 10-70% of viral isolations from middle ear fluid. In a study of infants aged 2-24 months with bronchiolitis, 86% had AOM; RSV was isolated from 71% of patients. In a majority of cases, viral infection of the nasopharynx and distal tubes cause Eustachian tube dysfunction, resulting in transient negative middle ear pressure, thus facilitating secondary viral or bacterial otitis media. The most common bacteria involved in the mixed RSV-bacterial infections are Streptococcus pneumoniae and Haemophilus influenzae. Further, there is evidence that enhanced synthesis of proinflammatory cytokines and cell adhesion molecules in the middle ear infected with RSV may contribute to the inflammatory processes in otitis media.
RSV is also very prevalent in the elderly, and along with influenza, a major cause of death, however, there is as yet no vaccine available to prevent death caused by RSV.
Rotavirus infection can cause gastroenteritis. It most often infects infants and young children. In children aged 3 months to 2 years, rotavirus is one of the most common causes of diarrhea, and hospitalisations. Rotavirus leads to outbreaks of diarrhea during the winter months and is particularly a problem in child-care centers and children's hospitals. Almost all children have had a rotavirus infection by the time they are 3 years old. Infected infants may experience a spectrum of symptoms ranging from vomiting, diarrhea, fever, dehydration and pain to more serious long-term complications such as lactose malabsorption, carbohydrate intolerance, early onset of protein intolerance and increased susceptibility to other infections. Rotavirus is a major cause of infant death in countries with poor public health systems.
Prevention of respiratory and intestinal infections has proven difficult, with very few vaccines available to prevent infections of the respiratory or intestinal tract, particularly in relation to RSV and rotavirus. Prevention of RSV infection in infants who are at high risk of death from RSV is attempted by the regular intramuscular injection of a monoclonal antibody. This monoclonal antibody has an effect in reducing the occurrence of serious cases of RSV in at risk children. However, it is highly invasive, very expensive, and only available to a small proportion of people at risk from RSV infection and the ongoing illness that can result.
Infants breast-fed with mother's milk have a reduced occurrence and a reduced severity of respiratory tract and intestinal tract infections. In the art, it is presently believed that this reduced occurrence and severity is partly because mother's milk contains immunoglobulin(s) with virus and/or other microorganism neutralizing activity.
Treatment of intestinal and respiratory infection is often difficult. Most cases are treated with palliative care only. Treatment for rotavirus infection is limited to oral and/or intravenous rehydration. Only a few effective drugs are available for respiratory infection and often treatment requires pulmonary administration of the drug. In young infants this leads to significant stress. Therefore there is a need for further effective agents that preferably can be administered without imposing stress, or with at least decreasing the amount of stress imposed on infants and children.
Some pathogens which gain entry to the body via the intestinal and/or respiratory tract are associated with systemic disease. For example, herpes virus can initially gain entry via the respiratory tract before invading and residing in other parts of the body to cause disease over time.
WO9613271 describes a composition for promoting gastrointestinal health comprises an effective amount of a beneficial human intestinal microorganism and an effective amount of an immunoglobulin composition comprising concentrated immunologically active immunoglobulins. Another composition for restoring and maintaining gastrointestinal health comprises 40-60% by weight of an immunoglobulin composition comprising concentrated immunologically active immunoglobulins and 40-60% by weight of soluble dietary fiber selected from inulin, fructo-oligosaccharides, pectin, guar gum, and mixtures thereof.